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How insulin aspart differs from human insulin is the change at position #28 in the B insulin chain; the natural amino acid present is Proline--insulin aspart substitutes aspartic acid for it. [2] This substitution reduces the tendency of the insulin to form hexamers. [3]

Preventing this self-association keeps the insulin in dimer and monomer form, making them absorb better and faster, resulting in faster onset, peak and less duration.

Insulin hexamers must break down into dimers and monomers to be absorbed. [4]

While insulin aspart has rapid-acting characteristics in humans, the insulin does not elicit the same response in dogs. [5] "Neither rat nor dog indicated the faster action of X14 (insulin aspart) or faster sc (subcutaneous) absorption, this could be shown in pigs and later in man." Novo Nordisk's documents discuss the fact that the skin of both dogs and rats contain less lipid (fat) than that of humans and pigs as a possibility for the lack of rapid action in the two species. [6]

A slight increase in alkaline phosphatase (ALP-liver values) [7] was noted in non-diabetic dogs treated with insulin aspart. The same increase was also noted in non-diabetic dogs treated with non-analog human insulin. The significance of this finding was declared unclear. Some humans treated with insulin aspart also presented higher ALP values. [8]

Dr. Nelson of University of California-Davis said in his lecture at the Ohio State Endocrinology Symposium in 2006 that if the short-acting analog insulins have any role in feline and canine diabetes, it is not yet determined. [9]